Evidence map›Paper›PMID 39245679›Full record

Trial reportEuropean journal of clinical nutrition2025

Association of leucine and other branched chain amino acids with clinical outcomes in malnourished inpatients: a secondary analysis of the randomized clinical trial EFFORT.

Carla Wunderle, Claudia Ciobanu, Jacqueline Ritz, Pascal Tribolet, Peter Neyer, Luca Bernasconi, Zeno Stanga, Beat Mueller, Philipp Schuetz

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02517476 (Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02517476 phase4completednot on this map

Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial: The EFFORT Trial

TypeinterventionalSponsorUniversity Hospital, Basel, SwitzerlandRan2014 to 2018Enrolled2,088ConditionsMalnutritionArmsNutritional therapy
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Carla Wunderle *Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.ORCID 0000-0003-1720-6462
Claudia Ciobanu *Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Jacqueline Ritz *Medical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Pascal TriboletMedical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Peter NeyerInstitute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.ORCID 0000-0002-8682-9578
Luca BernasconiInstitute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
Zeno StangaDivision of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Bern University Hospital and University of Bern, Bern, Switzerland.
Beat MuellerMedical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Philipp SchuetzMedical University Department, Division of General Internal and Emergency Medicine, Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau, Aarau, Switzerland. schuetzph@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe essential branched-chain amino acids leucine, isoleucine and valine are considered anabolic and stimulate protein synthesis in the muscles as well in the liver. They also promote muscle recovery and contribute to glucose homeostasis. Recent studies in critically ill patients have demonstrated that depletion of plasma leucine is associated with increased mortality, but data in the non-critical care setting is lacking.

methodsThis secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), investigated the impact of leucine, isoleucine, and valine metabolism on clinical outcomes. The primary endpoint was 180-day all-cause mortality.

resultsAmong 238 polymorbid patients with available metabolite measurements, low serum leucin levels were associated with a doubled risk of 180-day all-cause mortality in a fully adjusted regression model (adjusted HR 2.20 [95% CI 1.46-3.30], p < 0.001). There was also an association with mortality for isoleucine (1.56 [95% CI 1.03-2.35], p = 0.035) and valine (1.69 [95% CI 1.13-2.53], p = 0.011). When comparing effects of nutritional support on mortality in patients with high and low levels of leucine, there was no evidence of significant differences in effectiveness of the intervention. The same was true for isoleucine and valine.

conclusionOur data suggest that depletion of leucine, isoleucine, and valine among malnourished polymorbid patients is associated with increases in long-term mortality. However, patients with low metabolite levels did not show a pronounced benefit from nutritional support. Further research should focus on the clinical effects of nutritional support in patients with depleted stores of essential branched-chain amino acids. CLINICAL

trial registrationclinicaltrials.gov as NCT02517476 (registered 7 August 2015).

Indexed as

Amino Acids, Branched-ChainLeucineMalnutritionAgedAged, 80 and overFemaleHumansInpatientsIsoleucineMaleMiddle AgedNutritional SupportTreatment OutcomeAmino Acids, Branched-ChainIsoleucineLeucine

Identifiers

PMID39245679

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.